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Updated: Jun 1, 2026
Enrichment of Bruch's Membrane from Human Donor Eyes
Published on: November 15, 2015
C-reactive protein and complement factor H in aged human eyes and eyes with age-related macular degeneration
Imran A Bhutto1, Takayuki Baba, Carol Merges
1Department of Ophthalmology, Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, Maryland 21287-9115, USA.
Insights
Inflammation and complement factors C-reactive protein (CRP) and complement factor H (CFH) are implicated in age-related macular degeneration (AMD). This study found altered CRP and CFH distribution in AMD eyes, suggesting their role in disease pathogenesis.
Area of Science:
- Ophthalmology
- Immunology
- Pathology
Background:
- Inflammation and complement activation are increasingly recognized in age-related macular degeneration (AMD) pathogenesis.
- Genetic variations in complement factor H (CFH) and elevated C-reactive protein (CRP) levels are linked to AMD risk.
- This study investigated the localization of CRP and CFH in human donor eyes with and without AMD.
Purpose of the Study:
- To examine the immunolocalization of CRP and CFH in the macular region of human donor eyes.
- To compare the distribution and levels of CRP and CFH in aged control eyes versus eyes with AMD.
- To correlate the presence of CRP and CFH with pathological features in AMD.
Main Methods:
- Alkaline phosphatase immunohistochemistry was used to detect CRP and CFH in cryopreserved macular tissue sections.
- Polyclonal antibodies against CRP and CFH were employed.
- Three independent masked observers scored the immunostaining intensity.
Main Results:
- In control eyes, CRP and CFH were prominent in the retinal pigment epithelium/Bruch's membrane/choriocapillaris (RPE/BrM/CC) complex and intercapillary septa (ICS).
- AMD eyes showed significantly higher CRP and lower CFH levels in the BrM/CC/ICS complex compared to controls.
- Drusen and basal laminar deposits were intensely positive for both CRP and CFH, while their levels were reduced in geographical atrophy areas.
Conclusions:
- Significant alterations in CRP and CFH distribution and levels occur in early and late AMD.
- Elevated CRP and insufficient CFH at the retina/choroid interface may promote uncontrolled complement activation and tissue damage.
- These findings support the role of inflammation and immune-mediated processes in AMD pathogenesis.
Background:
There is increasing evidence that inflammation and immune-mediated processes (complement activation) play an important role in age-related macular degeneration (AMD) pathogenesis. A genetic variation in the gene encoding complement factor H (CFH) and plasma levels of C-reactive protein (CRP), a systemic marker of subclinical inflammation, have consistently been shown to be associated with an increased risk for AMD. In the present study, we examined the immunolocalisation of CRP and CFH in aged control human donor eyes (n=10; mean age 79 years) and eyes with AMD (n=18; mean age 83 years).
Methods:
Alkaline phosphatase immunohistochemistry was performed using polyclonal antibodies against CRP and CFH on cryopreserved tissue sections from disc/macular blocks. Three independent masked observers scored the reaction product (0-8).
Results:
In aged control eyes, the retinal pigment epithelium/Bruch's membrane/choriocapillaris (RPE/BrM/CC) complex including intercapillary septa (ICS) had the most prominent immunostaining for CRP and CFH. CRP was significantly higher than controls in BrM/CC/ICS and choroidal stroma in early and wet AMD eyes (p<0.05). In contrast, CFH was significantly lower in BrM/CC/ICS complex of AMD choroids than in controls (p<0.05). Interestingly, CRP and CFH were significantly reduced in BrM/CC/ICS complex in atrophic area of macula in geographical atrophy (p<0.05). Drusen and basal laminar deposits were intensely positive for CRP and CFH.
Conclusion:
These immunohistochemical findings show that changes in distribution and relative levels of CRP and CFH were evident in early and late AMD eyes. This suggests that high levels of CRP and insufficient CFH at the retina/choroid interface may lead to uncontrolled complement activation with associated cell and tissue damage. This study supports the hypothesis that inflammation and immune-mediated mechanisms are involved in the pathogenesis of AMD.
